Cerebral Small-Vessel Disease in Individuals with a Family History of Coronary Heart Disease: The Atherosclerosis Risk in Communities Study

Abstract

<b><i>Introduction:</i></b> The degree to which a family history of coronary heart disease (FHCHD) is associated with silent cerebral small-vessel disease (cSVD) among healthy adults, independent of prevalent CHD and traditional risk factors, is unknown. <b><i>Methods:</i></b> The Atherosclerosis Risk in Communities (ARIC) study is a community-based cohort study with self-reported family history data and brain magnetic resonance imaging (ages 68–88). The association between markers of cSVD (lacunar infarcts and cerebral microbleeds), or log-transformed white matter hyperintensity (WMH) volume, and FHCHD, or the number of affected relatives was examined using separate adjusted logistic or linear regression models, respectively. Race interaction terms were evaluated. <b><i>Results:</i></b> Of 1,639 participants without prevalent CHD (76 ± 5 years, 62% female, 29% black), 686 (42%) had FHCHD. There were higher odds of lacunar infarct (OR 1.40, 95% CI 1.07–1.84) among those with parental FHCHD and higher odds of microhemorrhages (lobar OR 1.86, 95% CI 1.13–3.06; subcortical OR 1.47, 95% CI 1.01–2.15) among those with sibling FHCHD. A greater number of any relative affected was associated with higher odds of lacunar infarct (OR 1.24, 95% CI 1.04–1.47) and lobar microhemorrhages (OR 1.31, 95% CI 1.05–1.64) but not subcortical microhemorrhages (OR 1.09, 95% CI 0.92–1.28). Odds of having a lacunar infarct were higher among blacks (p-interaction 0.04) with paternal FHCHD (OR 2.20, CI 1.35–3.58) than whites with paternal FHCHD (OR 1.17, CI 0.87–1.56). There was no association with WMH. <b><i>Discussion/Conclusion:</i></b> Markers of cSVD, specifically lacunar infarcts and microhemorrhages, appear to be associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.